The composition of the lung microbiome differs between patients with dermatomyositis and rheumatoid arthritis associated with interstitial lung disease

Abstract

Dermatomyositis and rheumatoid arthritis are inflammatory diseases that affect the skeletal muscles and joints, respectively. A common systemic complication of these diseases is interstitial lung disease (ILD), which leads to a poor prognosis and increased mortality. However, the mechanism for the initiation and development of ILD in patients with dermatomyositis is currently unknown. In the present study, we used 16S rRNA high-throughput sequencing to profile the bacterial community composition of bronchoalveolar lavage fluid of patients with dermatomyositis associated with ILD (DM-ILD; shortened to DM below), rheumatoid arthritis associated with ILD (RA-ILD; shortened to RA below) and healthy controls (N) aiming to understand the differences in their lung microbiota and to predict gene function. We found that there were more operational taxonomic units (OTUs) in the lung microbiota of both RA and DM compared to N, although there was no significant difference in the number of OTUs between RA and DM. Similarly, the diversity in alphaproteobacteria differed between RA and DM compared to N, but not between RA and DM. The lung microbiota of RA, DM and N was mainly comprised of five phyla: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria, with 10 dominant genera. Despite the similarity in microbiota composition, we also identified 41 OTUs of lung microbiota that differed among RA, DM and N. Additionally, linear discriminant analysis effect size and linear discriminant analysis genus scores confirmed that 31 microbial biomarkers were clearly distinguished among RA, DM and N. The functional and metabolic alterations of the lung microbiota among RA, DM and N were predicted using PICRUST, and differentially abundant KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways were identified. Research on the lung microbiota of patients with DM and RA may open new opportunities for developing biomarkers to identify high-risk patients.

Defining the baseline of pulmonary microbiota in healthy populations and influencing factors

“…In Fig. 1, we found the main bacterial phyla in the United States [32][33][34], Asia [35][36][37][38][39] and Europe [40][41][42][43] remain completely consistent. In the normal tissues of patients [44][45][46][47][48][49], four main bacterial phyla (Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes) were shared with healthy subjects.…”

“…In Fig. 5a, we found that Streptococcus, Prevotella, Veillonella are common to healthy and young populations [32,39,40] across three different continents (Asia Europe and North America). At the same time, while Neisseria is common to youth in the North America [32] and Europe [40], there are more than 20 gram-negative bacteria in the genus Neisseria, which can colonize mucosal surfaces and are often found in a healthy upper respiratory tract.…”

“…Furthermore, we found that Lachnospiraceae_incertae_sedis, Bacteroides, Hydrotalea, Staphylococcus, Enhydrobacter, Faecalibacterium, Blautia only appear in Asia, while Gemella, Granulicatella, Actinomyces are only found in Europe, which are absent from the composition of major pulmonary bacterial genera of healthy people on other continents (Asia and North America). The studies by Liu HX et al [35] and Lou Y et al's [39] Shanghai-based studies, all had exactly the same top ten bacterial genera in the lungs despite all the differences in age and sampling methods. They were Prevotella, Bacteroides, Streptococcus, Faecalibacterium, Enhydrobacter, Staphylococcus, Veillonella, Blautia, Lachnospiraceae, Hydratable.…”

“…In addition, Corynebacterium, which is considered as the part of the normal microbiota but also functions as a pathogen causing respiratory inflammatory diseases like tracheitis, pharyngitis, rhinosinusitis, bronchitis [52][53][54]. While in table S1, high frequency bacterial genera in healthy people [32,33,[35][36][37][39][40][41][42][43] are Veillonella, Streptococcus, Prevotella, Neisseria, Fusobacterium, Haemophilus. In Fig.…”

“…In Fig. 3a, we compared the studies from Asia [35][36][37]39] and found that the bacterial genera with the highest frequency are Veillonella, Streptococcus, Staphylococcus. In Fig.…”